Effect of Partial Portal Vein Ligation on Hepatic Regeneration

Abstract

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p < 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p < 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection. Keywords hepatic regeneration; portal hypertension; cirrhosis; liver growth; protal blood flow The origin and nature of the factors that control hepatic regeneration remain unresolved. Portal blood has been shown to be hepatotrophic as compared to peripheral blood. 1 However, controversy continues to surround the relative importance of the qualitative changes (hormonal factors) and the quantitative changes (blood flow parameters) in portal blood that occur after partial hepatectomy as they relate to the hepatic regeneration that occurs after a partial hepatic resection. 1-8 The pancreatic hormones, insulin and glucagon, have been shown to modulate, at least in part, the regenerative response that occurs after partial hepatectomy. 1-5 These data, however, do not negate an important role for hepatic blood flow, particularly portal venous blood flow, in the regulation of hepatic regeneration following partial hepatectomy. [6][7][8] The role of hepatic blood flow in modulating liver regeneration was first suggested by the observation that hepatic atrophy occurs after an Eck fistula (end-to-side portal caval shunt). 6 This hepatic atrophy was thought to be the result of a reduced hepatic blood flow,

Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis

“…Hepatocyte proliferation has been described when the liver is placed under stress [10], and ligation of portal vein branches was reported to induce hepatocyte growth factor expression [11]. However, with the increase in hepatocyte proliferation, we did not observe an increase in liver weight.…”

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation

“…This observation has also been demonstrated in our rodent models (personal unpublished data). Kahn et al [3] showed that rats with portal hypertension and diminished portal blood flow had a normal capacity to regenerate hepatic mass after hepatic resection. Uemura et al [4] also reported that after partial portal vein ligation, DNA synthesis in rats was significantly increased in the nonligated as compared with the ligated hepatic lobe.…”

Morbidity and Mortality of Hepatic Right Lobe Living Donors: Systematic Review and Perspectives

“…Khan et al [54] studied the effects of partial portal vein ligation 8 weeks prior to hepatectomy on a murine model of partial hepatectomy. They observed that partial portal vein ligation prior to hepatectomy did not impair hepatic regeneration capacity, compared to sham animals.…”